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Objective: The primary goal of this study was to determine in patients with normohormonal primary hyperparathyroidism (NHHPT) what percent reduction in post-excision intraoperative parathyroid hormone (IOPTH) from baseline would yield a rate of cure comparable to that in patients with classical primary hyperparathyroidism (PHPT)., Methods: This is a retrospective cohort study of patients who underwent parathyroidectomy between July 2013 and February 2020. Demographic data, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHHPT were compared to those with classical PHPT. Subgroup analyses were performed., Results: Of the 496 patients included in the study, 66 (13.3%) were of the normohormonal variant based on preoperative intact parathyroid hormone (PTH) levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the two normohormonal groups were not significantly different from their classical counterparts (98.4% and 100.0% vs. 97.1%, p = 1.000). The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.6% and 80.4% compared to their respective controls at 87.3%, p = 0.011 and p = 0.001. Although the rate of multiglandular disease was higher in one of the normohormonal variant groups, this difference was due to a higher rate of double adenomas, not four-gland hyperplasia., Conclusion: Patients with NHHPT undergoing parathyroidectomy can expect cure rates similar to that in patients with classical PHPT. The results of this study indicate that achieving an 80% drop or more in IOPTH levels predicts a high likelihood of cure. This is true irrespective of whether the patient is deemed normohormonal based on preoperative or intraoperative testing., Level of Evidence: 3 Laryngoscope, 134:2480-2484, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Virtual care utilization has increased in recent years bringing questions of how to best inform patients regarding their use. Decision aids (DAs) are tools created to assist patients in making informed decisions about their health care. This study seeks to determine whether a DA or previous experience could better educate and influence patient's preference on virtual care., Methods: One hundred fifty participants from an orthopedic clinic of a multi-hospital system were divided into three groups. Group 1 (Virtual Care Cohort) had at least one previous virtual care visit and was surveyed with the Telemedicine Satisfaction Questionnaire (TSQ). Group 2 (In-person with Decision Aid) and Group 3 (In-person without Decision Aid) had no virtual care experience. Group 2 received a validated virtual care DA with a knowledge test. Both groups were also administered the TSQ., Results: After the DA, patients improved their score on 3 of 4 virtual care knowledge questions. Each cohort demonstrated a positive perception of virtual care; however, the specific reasons for their favorable views varied. The DA cohort did not show increased preference toward virtual care compared with the non-DA group and only responded significantly higher regarding encounter comfort. Patients with previous experience in virtual care responded most favorably to the majority of survey questions regarding their virtual care preferences when compared with both virtual care naive cohorts., Discussion and Conclusion: We found that patient experience was the most important factor in influencing patient preference toward virtual care. Although the DA increased their virtual care knowledge it did not increase their preference; therefore, efforts should be placed at encouraging patient to experience virtual care., Competing Interests: No competing financial interests exist., (© Aaron R. Prater et al., 2024; Published by Mary Ann Liebert, Inc.)

Objectives: Unilateral clear thin rhinorrhea (UCTR) can be concerning for a nasal cerebrospinal fluid (CSF) leak. Beta-2 transferrin electrophoresis has been the gold standard for initial non-invasive confirmatory testing for CSF rhinorrhea, but there can be issues with fluid collection and testing errors. Ipratropium bromide nasal spray (IBNS) is highly effective at reducing rhinitis-related rhinorrhea, and should presumably not resolve CSF rhinorrhea. This study assessed whether different clinical features and IBNS response helped predict presence or absence of CSF rhinorrhea., Methods: A prospective cohort study was conducted where all patients with UCTR had nasal fluid tested for beta-2 transferrin, and were prescribed 0.06% IBNS. Patients were diagnosed with CSF rhinorrhea or other rhinologic conditions. Clinical variables like IBNS response (rhinorrhea reduction), positional worsening, salty taste, postoperative state, female gender, and body-mass index were assessed for their ability to predict CSF rhinorrhea. Sensitivity, specificity, and predictive values and odds ratios were calculated for all clinical variables., Results: Twenty patients had CSF rhinorrhea, and 53 had non-CSF etiologies. Amongst clinical variables assessed for predicting CSF absence or presence, significant associations were shown for IBNS response (OR = 844.66, p = 0.001), positional rhinorrhea worsening (OR = 8.22, p = 0.049), and body-mass index ≥30 (OR = 2.92, p = 0.048). IBNS response demonstrated 96% sensitivity and 100% specificity, and 100% positive and 91% negative predictive values for predicting CSF rhinorrhea., Conclusions: In patients with UCTR, 0.06% IBNS response is an excellent screening tool for excluding CSF rhinorrhea, and should be considered in the diagnostic workup of CSF rhinorrhea., Level of Evidence: 2 Laryngoscope, 134:56-61, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Key Points: Autonomic nerve densities were equivalent in posterior nasal (PNN), posterolateral nasal (PLNN), and anterior ethmoid nerves (AEN). Rhinitis studies should explore the utility of PLNN and/or AEN transection over PNN alone., (© 2023 ARS-AAOA, LLC.)

Purpose: Among patients in cardiac rehabilitation (CR) on beta-adrenergic blockade (βB) therapy, this study describes the frequency for which target heart rate (THR) values computed using a predicted maximal heart rate (HR max ), correspond to a THR computed using a measured HR max in the guideline-based heart rate reserve (HR reserve ) method., Methods: Before CR, patients completed a cardiopulmonary exercise test to measure HR max , with the data used to determine THR via the HR reserve method. Additionally, predicted HR max was computed for all patients using the 220 - age equation and two disease-specific equations, with the predicted values used to calculate THR via the straight percent and HR reserve methods. The THR was also computed using resting heart rate (HR) +20 and +30 bpm., Results: Mean predicted HR max using the 220 - age equation (161 ± 11 bpm) and the disease-specific equations (123 ± 9 bpm) differed ( P < .001) from measured HR max (133 ± 21 bpm). Also, THR computed using predicted HR max resulted in values that were infrequently within the guideline-based HR reserve range calculated using measured HR max . Specifically, 0 to ≤61% of patients would have had an exercise training HR that fell within the guideline-based range of 50-80% of measured HR reserve . Use of standing resting HR +20 or +30 bpm would have resulted in 100% and 48%, respectively, of patients exercising below 50% of HR reserve ., Conclusions: A THR computed using either predicted HR max or resting HR +20 or +30 bpm seldom results in a prescribed exercise intensity that is consistent with guideline recommendations for patients in CR., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In patients with heart failure with reduced ejection fraction (HFrEF), individual responses to beta-blockers vary. Candidate gene pharmacogenetic studies yielded significant but inconsistent results, and they may have missed important associations. Our objective was to use an unbiased genome-wide association study (GWAS) to identify loci influencing beta-blocker survival benefit in HFrEF patients. Genetic variant × beta-blocker exposure interactions were tested in Cox proportional hazards models for all-cause mortality stratified by self-identified race. The models were adjusted for clinical risk factors and propensity scores. A prospective HFrEF registry (469 black and 459 white patients) was used for discovery, and linkage disequilibrium (LD) clumped variants with a beta-blocker interaction of p < 5 × 10 -5 , were tested for Bonferroni-corrected validation in a multicenter HFrEF clinical trial (288 black and 579 white patients). A total of 229 and 18 variants in black and white HFrEF patients, respectively, had interactions with beta-blocker exposure at p < 5 × 10 -5 upon discovery. After LD-clumping, 100 variants and 4 variants in the black and white patients, respectively, remained for validation but none reached statistical significance. In conclusion, genetic variants of potential interest were identified in a discovery-based GWAS of beta-blocker survival benefit in HFrEF patients, but none were validated in an independent dataset. Larger cohorts or alternative approaches, such as polygenic scores, are needed.

Background: Multidisciplinary collaboration is essential for effective odontogenic sinusitis (ODS) management. One point of debate has been the optimal timing of primary dental treatment and endoscopic sinus surgery (ESS), but differences in time to completion of these treatment pathways have not been studied., Methods: A retrospective cohort study was conducted on ODS patients from 2015 to 2022. Demographic and clinical variables were recorded, and various durations of time were analyzed from rhinologic consultation through treatment completion. Resolution of sinusitis symptoms and purulence on endoscopy was also recorded., Results: Eighty-nine ODS patients were analyzed (47.2 % male, median 59 years-old). Of the 89 ODS patients, 56 had treatable dental pathology, and 33 had no treatable dental pathology. Median time to treatment completion for all patients was 103 days. Of 56 ODS patients with treatable dental pathology, 33 had primary dental treatment, and 27 (81 %) required secondary ESS. In patients who underwent primary dental treatment followed by ESS, median time from initial evaluation to treatment completion was 236.0 days. If ESS was pursued primarily followed by dental treatment, median time from initial evaluation to treatment completion was 112.0 days, which was significantly shorter than if dental treatment was pursued primarily (p = 0.002). Overall symptomatic and endoscopic resolution was 97.8 %., Conclusions: After dental and sinus surgical treatment, ODS patients experienced 97.8 % resolution of symptoms and purulence on endoscopy. In patients with ODS due to treatable dental pathology, primary ESS followed by dental treatment resulted in a shorter overall treatment duration than primary dental treatment followed by ESS., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Investigate the use of nasal endoscopy, sinus imaging, and neurologic evaluation in patients presenting to a rhinologist primarily for craniofacial pain., Methods: This was a retrospective analysis of consecutive outpatients presenting to a rhinologist between 2016 and 2019 with chief complaints of craniofacial pain with or without other sinonasal symptoms, who were then referred to and evaluated by headache specialists. Data analyzed included sinusitis symptoms, Sino-Nasal Outcome Test (SNOT-22) scores (and facial pain subscores), pain location, nasal endoscopy, computed tomography (CT) findings, and headache diagnoses made by headache specialists., Results: Of the 134 patients with prominent craniofacial pain, the majority of patients were diagnosed with migraine (50%) or tension-type (22%) headache, followed by multiple other non-sinogenic headache disorders. Approximately 5% of patients had headaches attributed to sinusitis. Amongst all patients, 90% had negative nasal endoscopies. Patients with negative endoscopies were significantly less likely to report smell loss ( P  = .003) compared to those with positive endoscopies. Poor agreement was demonstrated between self-reported pain locations and sinus findings on CT (kappa values < 0.20). Negative nasal endoscopy showed high concurrence with negative CT findings (80%-97%)., Conclusions: Patients presenting with chief complaints of craniofacial pain generally met criteria for various non-sinogenic headache disorders. Nasal endoscopy was negative in 90% of patients, and CT demonstrated poor agreement with pain locations. Nasal endoscopy and CT shared high concurrence rates for negative sinus findings. The value of nasal endoscopy over sinus imaging in craniofacial pain evaluation should be explored in future studies.

Objective: The aim of this research was to examine predictors and characterize causes of suicide death in people with traumatic brain injury (TBI) and conduct sensitivity analyses with and without people whose first diagnosis of TBI occurred within 3 days of their suicide death., Methods: This case-control study examined suicide risk for people with TBI in eight Mental Health Research Network-affiliated healthcare systems. Sample 1 included 61 persons with TBI who died by suicide and their 75 matched controls with TBI who did not die by suicide between January 1, 2000, and December 31, 2013. Sample 2 excluded the 34 persons with TBI whose first TBI diagnosis occurred within 3 days of their suicide death and their 46 matched controls. Descriptive statistics characterized the sample stratified by cases and controls, while conditional logistic regression models estimated the adjusted odds of suicide., Results: Over half of suicide deaths occurred within 3 days of a person's first diagnosis of TBI in the larger sample. After excluding these persons, people with TBI were 2.84 (95% confidence interval [CI]: 2.15-2.73) times more likely to die by suicide than were people without TBI. Among those with TBI, men were 16.39 times (95% CI: 1.89-142.15) more likely to die by suicide than were women., Conclusions: Accounting for TBI as a potential consequence of suicide attenuates the association between TBI and suicide, but a robust association persists-especially among men. Ultimately, all people with TBI should be carefully screened and monitored for suicide risk.HIGHLIGHTSPeople with traumatic brain injury (TBI) were at considerably elevated risk for suicide deathMen with TBI had significantly increased risk of suicide death compared to women with TBITBI timing suggests confusion of risk factors for and consequences of suicide.

Background: Patient-reported outcome measures (PROMs) are metrics that assess physical health, mental health, pain, and satisfaction. However, PROM collection in orthopaedic clinics presents numerous logistical and financial challenges. These challenges are reduced when PROMs are completed before clinic encounters, relieving the workflow constraints of in-office PROM collection. The purpose of this study was to determine the efficacy of 3 different methods with respect to pre-visit electronic PROM completion., Methods: Consecutive adult orthopaedic patients with no previous PROM participation were enrolled. Patients who registered with the electronic medical record (EMR) patient portal (MyChart) and with active e-mail addresses were randomly assigned to 1 of 3 arms: control (no pre-visit messages), MyChart (EMR patient portal pre-visit messages), and e-mail (e-mail pre-visit messages). The primary outcome measure was pre-visit PROM completion rates in orthopaedic patients, and the secondary outcome measures were time to pre-visit PROM form completion and PROM form completion rates according to patient demographic characteristics. By default, the Patient-Reported Outcomes Measurement Information System (PROMIS) forms were available for completion through the portal by 7 days before scheduled visits. Pre-visit messages were sent 7 days prior to the scheduled visit except in the control group, with reminders sent 3 days prior if still not completed. The patients in each arm who completed all assigned forms were labeled as having total PROM completion, and those who completed at least 1 completed form were considered as having partial PROM completion. Multivariable logistic regression models were used to assess differences in PROM completion rates between study arms. Kruskal-Wallis tests were performed to compare the date of the form completion., Results: A total of 291 patients were included. The pre-visit total completion rates for assigned PROMs were higher in the MyChart arm (49% of 97 patients; p = 0.005) and the e-mail arm (52% of 100 patients; p = 0.002) in comparison with the control arm (30% of 94 patients). Male patients were more likely than female patients to have partial pre-visit PROM completion (odds ratio [OR], 1.74; p = 0.03), and Caucasian patients were more likely to have partial pre-visit PROM completion than African American patients (OR, 2.28; p = 0.01)., Conclusions: Orthopaedic patients receiving either e-mail or patient portal messages demonstrated higher pre-visit PROM completion rates. Pre-visit messaging appears to be a useful strategy for increasing PROM completion rates and limiting the clinical workflow strain imposed by in-clinic PROM administration., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H321)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Study Objectives: Insomnia is associated with elevated levels of suicidal thoughts and behaviors. Emerging evidence suggests that cognitive-behavioral therapy for insomnia (CBTI) may reduce suicidal ideation (SI). However, the role of digital therapeutics in both the alleviation and prevention of SI remains unclear, and treatment mechanisms facilitating SI reductions have not been clearly identified., Methods: A total of 658 adults with Diagnostic and Statistical Manual of Mental Disorders, 5th Edition insomnia disorder enrolled in a single-site randomized controlled trial evaluating the efficacy of digital CBTI relative to attention control. Outcomes were measured at pretreatment, posttreatment, and 1-year follow-up., Results: Before treatment, 126 patients endorsed SI (19.1% prevalence). Among those with baseline SI, CBTI patients reported lower SI rates at posttreatment (30.0% vs 54.5%, p = .005) and 1-year follow-up (29.6% vs 46.8%, p = .042) relative to control. PRODCLIN analysis estimated that half of suicidolytic effects of CBTI were mediated through insomnia remission. Among those without baseline SI, CBTI did not directly prevent new onset SI. However, insomnia remitters reported lower rates of new-onset SI at posttreatment relative to non-remitters (1.5% vs 6.5%, p = .009). Mediation analysis supported a significant indirect effect wherein CBTI increased the likelihood of insomnia remission, which was associated with SI prevention (αβ = -3.20, 95% CI = -5.74 to -0.87)., Conclusion: Digital CBTI reduces insomnia symptoms, which promotes SI alleviation and prevention. For nonsuicidal patients, digital CBTI may serve as a highly accessible monotherapy for improving sleep, thereby reducing the risk for SI. For suicidal patients, digital CBTI may be appropriately administered as an adjunct treatment to support mainline intervention more directly targeting suicidogenic thoughts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prevention of major depressive disorder (MDD) is a public health priority. Strategies targeting individuals at elevated risk for MDD may guide effective preventive care. Insomnia is a reliable precursor to depression, preceding half of all incident and relapse cases. Thus, insomnia may serve as a useful entry point for preventing MDD. Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but widespread implementation is limited by a shortage of trained specialists. Innovative stepped-care approaches rooted in primary care can increase access to CBT-I and reduce rates of MDD., Methods/design: We propose a large-scale stepped-care clinical trial in the primary care setting that utilizes a sequential, multiple assignment, randomized trial (SMART) design to determine the effectiveness of dCBT-I alone and in combination with clinician-led CBT-I for insomnia and the prevention of MDD incidence and relapse. Specifically, our care model uses digital CBT-I (dCBT-I) as a first-line intervention to increase care access and reduce the need for specialist resources. Our proposal also adds clinician-led CBT-I for patients who do not remit with first-line intervention and need a more personalized approach from specialty care. We will evaluate negative repetitive thinking as a potential treatment mechanism by which dCBT-I and CBT-I benefit insomnia and depression outcomes., Discussion: This project will test a highly scalable model of sleep care in a large primary care system to determine the potential for wide dissemination and implementation to address the high volume of population need for safe and effective insomnia treatment and associated prevention of depression., Trial Registration: ClinicalTrials.gov NCT03322774. Registered on October 26, 2017., (© 2022. The Author(s).)

Background: Orbital, intracranial, and osseous extra-sinus complications can arise from bacterial or fungal sinusitis. Odontogenic sinusitis (ODS) can cause extra-sinus complications, but its prevalence remains poorly characterized., Objective: To determine the frequency of ODS as a cause of operative extra-sinus infectious complications and describe clinical features of all complicated sinusitis cases., Methods: A multi-institutional retrospective review was performed on all operative sinusitis-related extra-sinus complications from 2011 to 2020. ODS was diagnosed by sinus computed tomography (CT) and dental evaluations when available. Demographics, complication types, sinusitis etiologies, and various clinical features were analyzed., Results: Forty-five patients were included (mean age 55.5 years, 56% male). Of the extra-sinus complications, 40% were orbital only, 22% intracranial only, 13% osseous only, and 25% involved combined complications. The 2 most common causes of extra-sinus complications were ODS (40%) and mucopyocele (27%). When invasive fungal etiologies were excluded, and only unilateral maxillary opacification on CT was considered, nearly 60% of extra-sinus complications were due to ODS. Unilateral maxillary sinus opacification on CT was present in 100% of complicated ODS compared to 44% of nonodontogenic cases, and oral anaerobes were only identified in ODS cases. No complicated ODS patients underwent dental interventions during hospitalization., Conclusion: ODS was the most common cause of operative extra-sinus infectious complications. Clinicians should consider ODS high on the differential diagnosis of all patients presenting with complicated sinusitis, especially when sinusitis is unilateral and invasive fungal infection is not suspected.

Objective: Odontogenic sinusitis (ODS) can cause infectious orbital, intracranial, and osseous complications. Diagnosis and management of complicated ODS have not been discussed in recent sinusitis guidelines. The purpose of this systematic review was to describe epidemiological and clinical features, as well as management strategies of complicated ODS., Data Sources: PubMed, EMBASE, and Cochrane Library., Review Methods: A systematic review was performed to describe various features of complicated ODS. All complicated ODS studies were included in qualitative analysis, but studies were only included in quantitative analysis if they reported specific patient-level data., Results: Of 1126 studies identified, 75 studies with 110 complicated ODS cases were included in qualitative analysis, and 47 studies with 62 orbital and intracranial complications were included in quantitative analyses. About 70% of complicated ODS cases were orbital complications. Only 23% of complicated ODS studies were published in otolaryngology journals. Regarding ODS-related orbital and intracranial complications, about 80% occurred in adults, and 75% were male. Complicated ODS occurred most commonly from apical periodontitis of maxillary molars. There were no relationships between sinusitis extent and orbital or intracranial complications. High rates of anaerobic and α-hemolytic streptococcal bacteria were identified in complicated ODS. Management generally included systemic antibiotics covering aerobic and anaerobic bacteria, and surgical interventions were generally performed to address both the complications (orbital and/or intracranial) and possible infectious sources (dentition and sinuses)., Conclusion: ODS should be considered in all patients with infectious extrasinus complications. Multidisciplinary management between otolaryngologists, dental specialists, ophthalmologists, and neurosurgeons should be considered to optimize outcomes.

Background: The development of primary hyperparathyroidism (PHPT) after radioactive iodine (RAI) treatment for thyroid disease is poorly characterized. The current study is the largest reported cohort and assesses the disease characteristics of patients treated for PHPT with a history of RAI exposure., Methods: A retrospective analysis comparing patients, with and without a history of RAI treatment, who underwent surgery for PHPT., Results: Twenty-eight of the 469 patients had a history of RAI treatment, all for Graves' disease. Patients with a history of RAI exposure had similar disease characteristics compared to control; however, patients with a history of RAI treatment had a higher rate of recurrence (7.4% vs 1.2%, p = 0.012)., Conclusion: PHPT in patients with a history of RAI treatment can be approached in the same manner as RAI naive PHPT patients; however, the risk of recurrence of PHPT in RAI exposed patients may be higher., (© 2021 Wiley Periodicals LLC.)

Background: In the US, more than one million people attempt suicide each year. History of suicide attempt is a significant risk factor for death by suicide; however, there is a paucity of data from the US general population on this relationship. Aim: The objective of this study was to examine suicide attempts needing medical attention as a risk for suicide death. Method: We conducted a case-control study involving eight US healthcare systems. A total of 2,674 individuals who died by suicide from 2000 to 2013 were matched to 267,400 individuals by year and location. Results: Prior suicide attempt associated with a medical visit increases risk for suicide death by 39.1 times, particularly for women ( OR = 79.2). However, only 11.3% of suicide deaths were associated with an attempt that required medical attention. The association was the strongest for children 10-14 years old ( OR = 98.0). Most suicide attempts were recorded during the 20-week period prior to death. Limitations: Our study is limited to suicide attempts for which individuals sought medical care. Conclusion: In the US, prior suicide attempt is associated with an increased risk of suicide death; the risk is high especially during the period immediately following a nonlethal attempt.

Central line-associated bloodstream infections (CLABSIs) can result in increased morbidity and mortality and billions of dollars of costs per year to institutions and patients. Fluctuating availability of manufacturers' supplies of intravenous (IV) solutions have created issues for health systems in which policy and procedures have been examined regarding extended hang time for IV solutions. This article examined the relationship between extended hang times of nonadditive IV solutions and incidence of CLABSIs in intensive and general practice inpatient units in a quaternary care setting. The incidence of CLABSIs with extended hang times of up to 96 hours, of nonadditive IV solutions, has demonstrated that significant changes in CLABSIs were not evident., Competing Interests: The authors of this article have no conflicts of interest to disclose., (Copyright © 2021 Infusion Nurses Society.)

Purpose: To compare exercise training intensity during standard cardiac rehabilitation (S-CR) versus hybrid-CR (combined clinic- and remote home-/community-based)., Methods: The iATTEND (improving ATTENDance to cardiac rehabilitation) trial is currently enrolling subjects and randomizing patients to S-CR versus hybrid-CR. This substudy involves the first 47 subjects who completed ≥18 CR sessions. Patients in S-CR completed all visits in a typical phase II clinic-based setting and patients in hybrid-CR completed up to 17 of their sessions remotely using telehealth (TH). Exercise training intensity in both CR settings is based on heart rate (HR) data from each CR session, expressed as percent HR reserve., Results: Among patients in both study groups, there were no serious adverse events or falls that required hospitalization during or within 3 hr after completing a CR session. Expressed as a percentage of HR reserve, the overall mean exercise training intensities during both the S-CR sessions and the TH-CR sessions from hybrid-CR were not significantly different at 63 ± 12% and 65 ± 10%, respectively (P = .29)., Conclusion: This study showed that hybrid-CR delivered using remote TH results in exercise training intensities that are not significantly different from S-CR., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The policies of insurance carriers have used the truncal vein size as a criterion for coverage. The objective of the present study was to compare the effect of great saphenous vein (GSV) size ≥5 mm vs <5 mm on patient presentation and clinical outcomes., Methods: Patients in a national cohort were prospectively captured in the Vascular Quality Initiative Varicose Vein Registry. From January 2015 to October 2017, the Vascular Quality Initiative Varicose Vein Registry database was queried for all patients who had undergone varicose vein procedures. The CEAP (clinical, etiologic, anatomic, pathophysiologic) classification, Venous Clinical Severity Score, and patient-reported outcomes were compared by GSV size (<5 mm, group 1; ≥5 mm, group 2) before and after the procedures. A 2-sample Wilcoxon test was performed to assess the differences between the 2 groups stratified by GSV size. To assess for postoperative improvement, a matched-pairs Wilcoxon signed rank test was performed for each group separately., Results: During the study period, 5757 vein ablation procedures had been performed for GSV: 770 for GSV size <5 mm and 4987 for GSV size ≥5 mm. Patients in group 1 were more likely to be women (81.7% vs 68.4%; P = .001) and older (56.8 vs 55.6 years; P = .012). The CEAP clinical class was more advanced in group 2 than in group 1 (P = .001). The maximal GSV diameter in group 2 was significantly greater than in group 1 (8.32 vs 3.86 mm; P = .001); 64% of group 2 and 59.2% of group 1 had undergone radiofrequency thermal ablation (P = .001). No mortalities occurred in either group. Group 2 had more complications postoperatively (0.6% vs 0%; P = .027), required postoperative anticoagulation (8.8% vs 5%, P = .001), developed partial recanalization (0.8% vs 0.3%; P = .001), and missed more work days (2.32 vs 1.6 days) compared with group 1. A similar rate of hematoma developed in both groups, but group 1 had a higher rate of paresthesia. Both groups had improvement in the Venous Clinical Severity Score and HASTI (heaviness, achiness, swelling, throbbing, itching) score. The degree of symptomatic improvement between the 2 groups was similar., Conclusions: All patients demonstrated improvement in both clinical outcomes and patient-reported outcomes after endovenous ablation, regardless of GSV size. Patients with a preoperative GSV size ≥5 mm experienced similar improvement in symptoms but an increased complication rate. Patients with a smaller vein size should not be denied intervention or coverage by vein size., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine how the incorporation of specialty specific training for coders within a focused billing team affected revenue, efficiency, time to reimbursement, and physician satisfaction in an academic otolaryngology practice., Materials and Methods: Our academic otolaryngology department recently implemented a new billing system, which incorporated additional training in otolaryngology surgical procedures for medical coders. A mixed model analysis of variance was used to compare billing outcomes for the 6 months before and 6 months after this new approach was initiated. The following metrics were analyzed: Current Procedural Terminology codes, total charges, time between services rendered and billing submission, and time to reimbursement. A survey of department physicians assessing satisfaction with the system was reviewed., Results: There were 4087 Current Procedural Terminology codes included in the analysis. In comparing the periods before and after implementation of the new system, statistically significant decreases were found in the mean number of days to coding completion (19.3 to 12.0, respectively, p < 0.001), days to posting of charges (27.0 to 15.2, p < 0.001), days to final reimbursement (54.5 to 27.2, p < 0.001), and days to closure of form (179.2 to 76.6, p < 0.001). Physician satisfaction with communication and coder feedback increased from 36% to 64% after initiation of the new program., Conclusions: The implementation of additional specialty training for medical coders in the otolaryngology department of a large medical system was associated with improved revenue cycle efficiency. Additionally, this model appears to improve physician satisfaction and confidence with the coding system., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To determine the effect of intranasal Doyle splints on postoperative pain following septoplasty and inferior turbinate reduction (ITR). Changes in Nasal Obstruction Symptom Evaluation (NOSE) scores were also evaluated., Materials and Methods: A prospective cohort study conducted from January 2017 to January 2019. Patients were recruited if they experienced nasal obstruction due to septal deviation and inferior turbinate hypertrophy, and failed a one-month trial of intranasal corticosteroids. All patients underwent septoplasty with ITR, and either had Doyle splints or no splints placed. Patients were prescribed hydrocodone-acetaminophen 5-325 mg and asked to keep a daily log of pain medication use and visual analog scale (VAS) scores. Pain logs and NOSE scores were compared between patients who had splints versus patients who had no splints placed after septoplasty and ITR over the first postoperative week. NOSE scores were also collected at every postoperative visit (1 week, 1 month, and 6 months)., Results: Fifty-seven patients were enrolled (37 splints, 20 no-splints). The median postoperative pain VAS score was 3.0 (interquartile range [IQR] 2.0-5.0) for the splint group and 4.0 (IQR 2.0-5.0) for the no-splint group (P = 0.906). The median postoperative pain medication requirement in morphine equivalents at the first postoperative visit was 5.4 mg/day (IQR 2.0-13.3) for the splint group and 8.4 mg/day (IQR 1.8-15.3) for the no-splint group (P = 0.833)., Conclusions: There were no statistically significant differences in postoperative pain VAS scores or pain medication use between the two groups. All patients experienced significant reductions in NOSE scores postoperatively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Studies demonstrating mortality benefit of beta blockers (BB) after myocardial infarction (MI) were conducted before the era of percutaneous intervention and widespread use of statins. Recent retrospective studies show inconsistent results regarding which subgroups of coronary artery disease (CAD) patients' benefit. Most studies did not account for medication changes over time. We evaluated the association of time-varying BB exposure with death in CAD patients with or without a history of MI., Methods: This retrospective cohort study included all patients with MI and those with coronary disease but no MI at a single health care system who also had health insurance from January 1, 1997, to June 30, 2011. Pharmacy claims data were used to estimate BB exposure over 6-month rolling windows. The primary endpoint was all-cause death. The effect of BB exposure was tested using time-updated Cox proportional hazards models., Results: We identified 6220 patients with MI and 21,285 patients with CAD but no MI. Among patients who suffered MI, BB exposure was associated with a 31% relative risk reduction in all-cause death (hazard ratio [HR] 0.69, P = 0.001). Among subjects who survived 3 years after MI, BB retained a protective association (HR 0.71, P = 0.001). Among CAD-only patients, BB exposure was also associated with risk reduction (HR 0.85, P = 0.001)., Conclusion: Among patients with CAD, BB exposure is associated with reduced risk of death. The association is strongest among those who have suffered MI. This favorable association appears durable beyond 3 years.

Background: Prior research suggests that substance use disorders (SUDs) are associated with risk of suicide mortality, but most previous work has been conducted among Veterans Health Administration patients. Few studies have examined the relationship between SUDs and suicide mortality in general populations. Our study estimates the association of SUDs with suicide mortality in a general US population of men and women who receive care across eight integrated health systems., Methods: We conducted a case-control study using electronic health records and claims data from eight integrated health systems of the Mental Health Research Network. Participants were 2674 men and women who died by suicide between 2000-2013 and 267,400 matched controls. The main outcome was suicide mortality, assessed using data from the health systems and confirmed by state death data systems. Demographic and diagnostic data on substance use disorders and other health conditions were obtained from each health system. First, we compared descriptive statistics for cases and controls, including age, gender, income, and education. Next, we compared the rate of each substance use disorder category for cases and controls. Finally, we used conditional logistic regression models to estimate unadjusted and adjusted odds of suicide associated with each substance use disorder category., Results: All categories of substance use disorders were associated with increased risk of suicide mortality. Adjusted odds ratios ranged from 2.0 (CI 1.7, 2.3) for patients with tobacco use disorder only to 11.2 (CI 8.0, 15.6) for patients with multiple alcohol, drug, and tobacco use disorders. Substance use disorders were associated with increased relative risk of suicide for both women and men across all categories, but the relative risk was more pronounced in women., Conclusions: Substance use disorders are associated with significant risk of suicide mortality, especially for women, even after controlling for other important risk factors. Experiencing multiple substance use disorders is particularly risky. These findings suggest increased suicide risk screening and prevention efforts for individuals with substance use disorders are needed.

Purpose: Protein kinase C alpha (gene: PRKCA) is a key regulator of cardiac contractility. Two genetic variants have recently been discovered to regulate PRKCA expression in failing human heart tissue (rs9909004 [T → C] and rs9303504 [C → G]). The association of those variants with clinical outcomes in patients with heart failure (HF), and their interaction with HF drug efficacy, is unknown., Methods: Patients with HF in a prospective registry starting in 2007 were genotyped by whole genome array (n = 951). The primary outcome was all-cause mortality. Cox proportional hazards models adjusted for established clinical risk factors and genomic ancestry tested the independent association of rs9909004 or rs9303504 and the variant interactions with cornerstone HF pharmacotherapies (beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) in additive genetic models., Results: The minor allele of rs9909004, but not of rs9303504, was independently associated with a decreased risk for all-cause mortality: adjusted HR = 0.81 (95% CI = 0.67-0.98), p = 0.032. The variants did not significantly interact with mortality benefit associated with cornerstone HF pharmacotherapies (p > 0.1 for all)., Conclusions: A recently discovered cardiac-specific regulatory variant for PRKCA (rs9909004) was independently associated with a decreased risk for all-cause mortality in patients with HF. The variant did not interact with mortality benefit associated with cornerstone HF pharmacotherapies.

Background: The United States has experienced a significant rise in suicide. As decision makers identify how to address this national concern, healthcare systems have been identified as an optimal location for prevention., Objective: To compare variation in patterns of healthcare use, by health setting, between individuals who died by suicide and the general population., Design: Case-Control Study., Setting: Eight healthcare systems across the United States., Participants: 2674 individuals who died by suicide between 2000 and 2013 along with 267,400 individuals matched on time-period of health plan membership and health system affiliation., Measurements: Healthcare use in the emergency room, inpatient hospital, primary care, and outpatient specialty setting measured using electronic health record data during the 7-, 30-, 60-, 90-, 180-, and 365-day time periods before suicide and matched index date for controls., Results: Healthcare use was more common across all healthcare settings for individuals who died by suicide. Nearly 30% of individuals had a healthcare visit in the 7-days before suicide (6.5% emergency, 16.3% outpatient specialty, and 9.5% primary care), over half within 30 days, and >90% within 365 days. Those who died by suicide averaged 16.7 healthcare visits during the year. The relative risk of suicide was greatest for individuals who received care in the inpatient setting (aOR = 6.23). There was both a large relative risk (aOR = 3.08) and absolute utilization rate (43.8%) in the emergency room before suicide., Limitations: Participant race/ethnicity was not available. The sample did not include uninsured individuals., Conclusions: This study provides important data about how care utilization differs for those who die by suicide compared to the general population and can inform decision makers on targeting of suicide prevention activities within health systems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Although mental health conditions are risk factors for suicide, limited data are available on suicide mortality associated with specific mental health conditions in the U.S. population. This study aimed to fill this gap., Methods: This study used a case-control design. Patients in the case group were those who died by suicide between 2000 and 2013 and who were patients in eight health care systems in the Mental Health Research Network (N=2,674). Each was matched with 100 general population patients from the same system (N=267,400). Diagnostic codes for five mental health conditions in the year before death were obtained from medical records: anxiety disorders, attention deficit-hyperactivity disorder (ADHD), bipolar disorder, depressive disorders, and schizophrenia spectrum disorder., Results: Among patients in the case group, 51.3% had a recorded psychiatric diagnosis in the year before death, compared with 12.7% of control group patients. Risk of suicide mortality was highest among those with schizophrenia spectrum disorder, after adjustment for age and sociodemographic characteristics (adjusted odds ratio [AOR]=15.0) followed by bipolar disorder (AOR=13.2), depressive disorders (AOR=7.2), anxiety disorders (AOR=5.8), and ADHD (AOR=2.4). The risk of suicide death among those with a diagnosed bipolar disorder was higher in women than men., Conclusions: Half of those who died by suicide had at least one diagnosed mental health condition in the year before death, and most mental health conditions were associated with an increased risk of suicide. Findings suggest the importance of suicide screening and providing an approach to improve awareness of mental health conditions.

Background: Postoperative arterial epistaxis and sphenoid sinus stenosis after sphenoidotomies for endoscopic sinus surgery (ESS) and transsphenoidal approaches (TSAs) are uncommon. One potential source of epistaxis after sphenoidotomy is the sphenopalatine artery's posterior septal branch (PSB). PSB injury, in addition to other factors, could increase the risk of sphenoid stenosis. The purpose of this study was to determine incidence of, and risks factors for, the following outcomes after sphenoidotomy: PSB injury; postoperative epistaxis from the injured PSB; and sphenoid stenosis after PSB injury., Methods: A single-institution, prospective case series was conducted based on 233 sphenoidotomies performed during ESS (n = 163) and TSAs (n = 70). Outcome measures included intraoperative PSB injury, postoperative epistaxis from the PSB, and sphenoid stenosis., Results: The incidence of PSB injury was 17.2% during ESS-related sphenoidotomies, and 5.7% during TSA-related sphenoidotomies (p = 0.010). After PSB injury during ESS- and TSA-related sphenoidotomies (n = 32), there was 1 instance of epistaxis from the PSB (3.1%). Of the 161 ESS-related sphenoidotomies, 6 developed complete or near-complete stenosis (3.7%), which was more likely to occur with smaller anterior sphenoid face dimensions (p = 0.001). PSB injury, revision sphenoidotomy, and other factors did not increase the risk of stenosis. None of the TSA-related sphenoidotomies stenosed completely. Median follow-up was 7 months., Conclusion: PSB injury occurred in 17.2% of ESS-related sphenoidotomies and 5.8% of TSA-related sphenoidotomies. After PSB injury, postoperative epistaxis from the PSB was rare (3.1%). After ESS-related sphenoidotomies, sphenoid stenosis was rare (3.7%), and was more likely to occur with smaller sphenoid dimensions, but not with PSB injury or other factors., (© 2019 ARS-AAOA, LLC.)

Background: Risk stratification is critical in heart failure (HF) and the Meta-Analysis Global Group in Chronic HF (MAGGIC) score is a validated tool derived from ~40,000 patients. However, few of these patients self-identified as black, raising uncertainty regarding performance in blacks with HF., Methods and Results: This study analyzed a racially diverse group of 4046 patients (1646 black and 2400 white) from a single center from 2007 to 2015. Baseline characteristics were collected to tabulate MAGGIC score and test its discrimination and calibration within race groups. The primary end point was all-cause mortality. Death was detected using system records and the social security death master file. Discrimination was tested using Cox models of MAGGIC score stratified by race, and combined analysis including MAGGIC, race, and MAGGIC×race. Calibration was assessed using linear regression models and plots of observed versus predicted data. Overall, 901 (21%) patients died during 1-year follow-up. MAGGIC score discrimination was similar in both race groups in terms of C statistic (0.707±0.027 versus 0.725±0.014, for black versus white; P=0.556) and the hazard ratio (HR) per MAGGIC point was 1.12 in black patients (95% CI, 1.10-1.14) and 1.13 in white patients (95% CI, 1.12-1.14). Race was a significant correlate of survival, with better survival in black patients compared with white (HR, 0.66; 95% CI, 0.56-0.78), but the interaction of MAGGIC×race was not significant (β=-0.013; P=0.16), and adding race to the model did not improve discrimination (C statistic for MAGGIC versus MAGGIC+race, 0.721 versus 0.722; P=0.79). In calibration testing, the slope was not significantly different from 1 in either group, but the groups differed from each other, and it was closer to unity among black patients (0.94 versus 1.4; P=0.004)., Conclusions: These data support the use of the MAGGIC score to risk stratify black patients with HF.

The antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is released from thymosin-β4 (Tβ4) by the meprin-α and prolyl oligopeptidase (POP) enzymes and is hydrolyzed by angiotensin-converting enzyme (ACE). Ac-SDKP is present in urine; however, it is not clear whether de novo tubular release occurs or if glomerular filtration is the main source. We hypothesized that Ac-SDKP is released into the lumen of the nephrons and that it exerts an antifibrotic effect. We determined the presence of Tβ4, meprin-α, and POP in the kidneys of Sprague-Dawley rats. The stop-flow technique was used to evaluate Ac-SDKP formation in different nephron segments. Finally, we decreased Ac-SDKP formation by inhibiting the POP enzyme and evaluated the long-term effect in renal fibrosis. The Tβ4 precursor and the releasing enzymes meprin-α and POP were expressed in the kidneys. POP enzyme activity was almost double that in the renal medulla compared with the renal cortex. With the use of the stop-flow technique, we detected the highest Ac-SDKP concentrations in the distal nephron. The infusion of a POP inhibitor into the kidney decreased the amount of Ac-SDKP in distal nephron segments and in the proximal nephron to a minor extent. An ACE inhibitor increased the Ac-SDKP content in all nephron segments, but the increase was highest in the distal portion. The chronic infusion of a POP inhibitor increased kidney medullary fibrosis, which was prevented by Ac-SDKP. We conclude that Ac-SDKP is released by the nephron and is part of an important antifibrotic system in the kidney.

Background: The authors compared proportions and associations of depression screening, major depression, and follow-up care of Arab Americans compared to non-Hispanic whites, non-Hispanic blacks, Asians, and Hispanics., Methods: Administrative data was electronically abstracted from a large health system in metropolitan Detroit among 97,918 adult patients in 2014 and 2015. A valid and reliable surname list was used to identify Arab Americans. Using chi-squares, we examined the relationship between race/ethnicity and depression screening, major depression, and follow-up care. We calculated odds ratios (OR) and 95% confidence intervals (CI) to examine the relationship between the main independent variable of race/ethnicity and the dependent variables of depression screening and major depression while controlling for confounders., Results: Arab American women were 23% less likely to be screened for depression compared to non-Hispanic white women (OR = 0.77; 95% CI = 0.70, 0.86). The age- and sex-adjusted proportions of major depression were 5.5% for Arab Americans compared to 7.0% for Hispanics, 6.0% for non-Hispanic blacks, 5.9% for non-Hispanic whites, and 1.5% for Asians. Arab Americans with major depression were less likely to follow up with a behavioral specialist and more likely to follow up with a primary care physician compared to other racial and ethnic groups., Conclusions: Our study adds to the discourse on depression care among Arab Americans by highlighting the existing disparities related to adequate screening and appropriate management of depression. Future studies should include information about the influences of acculturation, culture, stigma, family, and religion on depression care., (© 2018 Wiley Periodicals, Inc.)

Zucker obese rats (ZOR) have higher glomerular capillary pressure (P GC ) that can cause renal damage. P GC is controlled by afferent (Af-Art) and efferent arteriole (Ef-Art) resistance. Af-Art resistance is regulated by factors that regulate other arterioles, such as myogenic response. In addition, it is also regulated by 2 intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that increased CTGF contributes to TGF attenuation, which in turn increases P GC in ZOR. We performed a renal micropuncture experiment and measured stop-flow pressure (P SF ), which is an indirect measurement of P GC in ZOR. Maximal TGF response at 40 nl/min was attenuated in ZOR (4.47 ± 0.60 mmHg) in comparison to the Zucker lean rats (ZLR; 8.54 ± 0.73 mmHg, P < 0.05), and CTGF was elevated in ZOR (5.34 ± 0.87 mmHg) compared with ZLR (1.12 ± 1.28 mmHg, P < 0.05). CTGF inhibition with epithelial sodium channel blocker normalized the maximum P SF change in ZOR indicating that CTGF plays a significant role in TGF attenuation (ZOR, 10.67 ± 1.07 mmHg vs. ZLR, 9.5 ± 1.53 mmHg). We conclude that enhanced CTGF contributes to TGF attenuation in ZOR and potentially contribute to progressive renal damage.

Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (P GC ) that can cause significant glomerular injury in the remnant kidney. P GC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa; and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC). Resetting of TGF post-UNx can allow systemic pressure to be transmitted to the glomerulus and cause renal damage, but the mechanism behind this resetting is unclear. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that CTGF is increased after UNx and contributes to TGF resetting. To test this hypothesis, we performed UNx in Sprague-Dawley (8) rats. Twenty-four hours after surgery, we performed micropuncture of individual nephrons and measured stop-flow pressure (P SF ). P SF is an indirect measurement of P GC . Maximal TGF response at 40 nl/min was 8.9 ± 1.24 mmHg in sham-UNx rats and 1.39 ± 1.02 mmHg in UNx rats, indicating TGF resetting after UNx. When CTGF was inhibited with the ENaC blocker benzamil (1 μM/l), the TGF response was 12.29 ± 2.01 mmHg in UNx rats and 13.03 ± 1.25 mmHg in sham-UNx rats, indicating restoration of the TGF responses in UNx. We conclude that enhanced CTGF contributes to TGF resetting after UNx.

Background: Obesity is a public health problem, associated with salt sensitive hypertension, kidney inflammation, and fibrosis. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a tetra peptide with anti-inflammatory and anti-fibrotic properties. However, its effect on preventing kidney damage in obesity is unknown. We hypothesized that Zucker obese (ZO) rats on a high-salt (HS) diet develop renal damage, inflammation, fibrosis, and this is prevented with Ac-SDKP treatment., Methods: Zucker lean (ZL) and ZO rats (8 weeks old) were treated with Ac-SDKP (1.6 mg/kg/day) while maintained on either a normal-salt (NS; 0.4%) or HS (4%) diet for 8 weeks. Systolic blood pressure (SBP), albuminuria, renal inflammation, and fibrosis were evaluated., Results: HS diet increased macrophage infiltration in the kidneys of both ZL and ZO rats but was significantly higher in ZO rats receiving the HS diet (ZL + NS, 13.9 ± 1.3 vs. ZL + HS, 19.14 ± 1.5 and ZO + NS, 25.5 ± 1.4 vs. ZO + HS, 87.8 ± 10.8 cells/mm2; P < 0.05). Ac-SDKP prevented macrophage infiltration in ZO rats (ZO + HS + Ac-SDKP, 32.18 ± 2.4 cells/mm2; P < 0.05). Similarly, glomerulosclerosis, cortical, and medullary interstitial fibrosis were increased in ZO rats fed the HS diet, and Ac-SDKP attenuated these alterations (P < 0.05). SBP was increased in ZO rats fed the HS diet (ZO + NS, 121.3 ± 8.9 vs. ZO + HS, 164 ± 6.9 mm Hg; P < 0.05), and it was significantly decreased with Ac-SDKP treatment (ZO + HS + Ac-SDKP, 144.05 ± 14.1 mm Hg; P = 0.004). Albuminuria was higher in ZO rats than in ZL rats; however, neither HS nor Ac-SDKP treatment affected it., Conclusions: Ac-SDKP treatment in ZO rats fed a HS diet prevented renal damage by reducing inflammation, fibrosis, and SBP.

Thymosin β4 (Tβ4), a ubiquitous peptide, regulates several cellular processes that include cell morphology, wound healing, and inflammatory response. Administration of exogenous Tβ4 is protective in diabetic nephropathy and in a unilateral ureteral obstruction model. However, the role of endogenous Tβ4 in health and disease conditions remains unclear. To elucidate the pathophysiological role of endogenous Tβ4 in hypertension, we examined angiotensin-II (Ang-II)-induced renal and cardiac damage in Tβ4 knockout (Tβ4 KO) mice. Tβ4 KO and wild-type C57BL/6 mice were infused continuously for 6 weeks with either vehicle or Ang-II (980 ng/kg per minute). At baseline, Tβ4 deficiency did not affect renal and cardiac function. Systolic blood pressure in the Ang-II group was similar in wild-type and Tβ4 KO mice (wild-type Ang-II, 179.25±10.11 mm Hg; Tβ4 KO Ang-II, 169.81±6.54 mm Hg). Despite the similar systolic blood pressure after Ang-II infusion, Tβ4-deficient mice had dramatically increased albuminuria and decreased nephrin expression in the kidney ( P <0.005). In the heart of Tβ4 KO mice, Ang-II reduced ejection fraction and shortening fraction (ejection fraction: wild-type Ang-II 77.95%±1.03%; Tβ4 KO Ang-II 62.58%±3.25%; P <0.005), which was accompanied by cardiac hypertrophy and left ventricular dilatation. In addition, renal and cardiac infiltration of CD68 macrophages, intercellular adhesion molecule-1, and total collagen content were increased after Ang-II infusion in Tβ4 KO mice ( P <0.005). Overall, our data indicate that endogenous Tβ4 is crucial in preventing tissue injury from Ang-II-induced hypertension. This study gives new insights into the protective role of endogenous Tβ4 in hypertensive end-organ damage., (© 2018 American Heart Association, Inc.)

Objective: Mitigation of suicide risk by reducing access to lethal means, such as firearms and potentially lethal medications, is a highly recommended practice. To better understand groups of patients at risk of suicide in medical settings, the authors compared demographic and clinical risk factors between patients who died by suicide by using firearms or other means with matched patients who did not die by suicide (control group)., Methods: In a case-control study in 2016 from eight health care systems within the Mental Health Research Network, 2,674 suicide cases from 2010-2013 were matched to a control group (N=267,400). The association between suicide by firearm or other means and medical record information on demographic characteristics, general medical disorders, and mental disorders was assessed., Results: The odds of having a mental disorder were higher among cases of suicide involving a method other than a firearm. Fourteen general medical disorders were associated with statistically significant (p<.001) greater odds of suicide by firearm, including traumatic brain injury (TBI) (odds ratio [OR]=23.53), epilepsy (OR=3.17), psychogenic pain (OR=2.82), migraine (OR=2.35), and stroke (OR=2.20). Fifteen general medical disorders were associated with statistically significant (p<.001) greater odds of suicide by other means, with particularly high odds for TBI (OR=7.74), epilepsy (OR=3.28), HIV/AIDS (OR=6.03), and migraine (OR=3.17)., Conclusions: Medical providers should consider targeting suicide risk screening for patients with any mental disorder, TBI, epilepsy, HIV, psychogenic pain, stroke, and migraine. When suicide risk is detected, counseling on reducing access to lethal means should include both firearms and other means for at-risk groups.

The natural peptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) decreases inflammation in chronic diseases such as hypertension and heart failure. However, Ac-SDKP effects on acute inflammatory responses during myocardial infarction (MI) are unknown. During the first 72 hours post-MI, neutrophils, M1 macrophages (pro-inflammatory), and M2 macrophages (pro-resolution) and release of myeloperoxidase (MPO) and matrix metalloproteinases (MMP) are involved in cardiac rupture. We hypothesized that in the acute stage of MI, Ac-SDKP decreases the incidence of cardiac rupture and mortality by preventing immune cell infiltration as well as by decreasing MPO and MMP expression. MI was induced by ligating the left descending coronary artery in C57BL/6 mice. Vehicle or Ac-SDKP (1.6 mg/kg/d) was infused via osmotic minipump. Cardiac immune cell infiltration was assessed by flow cytometry, cardiac MPO and MMP levels were measured at 24-48 hrs post-MI. Cardiac rupture and mortality incidence were determined at 7 days post-MI. In infarcted mice, Ac-SDKP significantly decreased cardiac rupture incidence from 51.0% (26 of 51 animals) to 27.3% (12 of 44) and mortality from 56.9% (29 of 51) to 31.8% (14 of 44). Ac-SDKP reduced M1 macrophages in cardiac tissue after MI, without affecting M2 macrophages and neutrophils. Ac-SDKP decreased MMP-9 activation in infarcted hearts with no changes on MPO expression. Ac-SDKP prevents cardiac rupture and decreases mortality post-acute MI. These protective effects of Ac-SDKP are associated with decreased pro-inflammatory M1 macrophage infiltration and MMP-9 activation.

Renal blood flow (RBF) provides important information regarding renal physiology and nephropathies. Arterial spin labeling-magnetic resonance imaging (ASL-MRI) is a noninvasive method of measuring blood flow without exogenous contrast media. However, low signal-to-noise ratio and respiratory motion artifacts are challenges for RBF measurements in small animals. Our objective was to evaluate the feasibility and reproducibility of RBF measurements by ASL-MRI using respiratory-gating and navigator correction methods to reduce motion artifacts. ASL-MRI images were obtained from the kidneys of Sprague-Dawley (SD) rats on a 7-Tesla Varian MRI system with a spin-echo imaging sequence. After 4 days, the study was repeated to evaluate its reproducibility. RBF was also measured in animals under unilateral nephrectomy and in renal artery stenosis (RST) to evaluate the sensitivity in high and low RBF models, respectively. RBF was also evaluated in Dahl salt-sensitive (SS) rats and spontaneous hypertensive rats (SHR). In SD rats, the cortical RBFs (cRBF) were 305 ± 59 and 271.8 ± 39 ml·min -1 ·100 g tissue -1 in the right and left kidneys, respectively. Retest analysis revealed no differences ( P = 0.2). The test-retest reliability coefficient was 92 ± 5%. The cRBFs before and after the nephrectomy were 296.8 ± 30 and 428.2 ± 45 ml·min -1 ·100 g tissue -1 ( P = 0.02), respectively. The kidneys with RST exhibited a cRBF decrease compared with sham animals (86 ± 17.6 vs. 198 ± 33.7 ml·min -1 ·100 g tissue -1 ; P < 0.01). The cRBFs in SD, Dahl-SS, and SHR rats were not different ( P = 0.35). We conclude that ASL-MRI performed with navigator correction and respiratory gating is a feasible and reliable noninvasive method for measuring RBF in rats.

Background: Patients diagnosed with skin conditions have a higher risk of comorbid psychiatric conditions and suicide-related outcomes such as suicidal ideations and behaviors. There is paucity of evidence in the US general population about the risk of suicide death in patients with dermatologic conditions., Methods: We conducted a retrospective case-control study to investigate the risk of suicide death in patients receiving care for dermatologic conditions. This study involved 8 US health systems. A total of 2674 individuals who died by suicide (cases) were matched with 267,400 general population control individuals., Results: After adjusting for age, sex, and any mental health or substance use condition, we did not find an association between death by suicide and any skin condition including conditions where clinicians are generally concerned about the risk such as acne (adjusted odds ratio [aOR] = 1.04, p = 0.814), atopic dermatitis (aOR = 0.77, p = 0.28), and psoriasis (aOR = 0.91, p = 0.64)., Conclusion: This case-control study provides no evidence of increased risk of death by suicide in individuals with major skin disorders in the US general population., (Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Afferent arteriole (Af-Art) resistance is modulated by two intrinsic nephron feedbacks: 1 ) the vasoconstrictor tubuloglomerular feedback (TGF) mediated by Na + -K + -2Cl - cotransporters (NKCC2) in the macula densa and blocked by furosemide and 2 ) the vasodilator connecting tubule glomerular feedback (CTGF), mediated by epithelial Na + channels (ENaC) in the connecting tubule and blocked by benzamil. High salt intake reduces Af-Art vasoconstrictor ability in Dahl salt-sensitive rats (Dahl SS). Previously, we measured CTGF indirectly, by differences between TGF responses with and without CTGF inhibition. We recently developed a new method to measure CTGF more directly by simultaneously inhibiting NKCC2 and the Na + /H + exchanger (NHE). We hypothesize that in vivo during simultaneous inhibition of NKCC2 and NHE, CTGF causes an Af-Art dilatation revealed by an increase in stop-flow pressure (P SF ) in Dahl SS and that is enhanced with a high salt intake. In the presence of furosemide alone, increasing nephron perfusion did not change the P SF in either Dahl salt-resistant rats (Dahl SR) or Dahl SS. When furosemide and an NHE inhibitor, dimethylamiloride, were perfused simultaneously, an increase in tubular flow caused Af-Art dilatation that was demonstrated by an increase in P SF. This increase was greater in Dahl SS [4.5 ± 0.4 (SE) mmHg] than in Dahl SR (2.5 ± 0.3 mmHg; P < 0.01). We confirmed that CTGF causes this vasodilation, since benzamil completely blocked this effect. However, a high salt intake did not augment the Af-Art dilatation. We conclude that during simultaneous inhibition of NKCC2 and NHE in the nephron, CTGF induces Af-Art dilatation and a high salt intake failed to enhance this effect., (Copyright © 2017 the American Physiological Society.)

Introduction: Most individuals make healthcare visits before suicide, but many do not have a diagnosed mental health condition. This study seeks to investigate suicide risk among patients with a range of physical health conditions in a U.S. general population sample and whether risk persists after adjustment for mental health and substance use diagnoses., Methods: This study included 2,674 individuals who died by suicide between 2000 and 2013 along with 267,400 controls matched on year and location in a case-control study conducted in 2016 across eight Mental Health Research Network healthcare systems. A total of 19 physical health conditions were identified using diagnostic codes within the healthcare systems' Virtual Data Warehouse, including electronic health record and insurance claims data, during the year before index date., Results: Seventeen physical health conditions were associated with increased suicide risk after adjustment for age and sex (p<0.001); nine associations persisted after additional adjustment for mental health and substance use diagnoses. Three conditions had a more than twofold increased suicide risk: traumatic brain injury (AOR=8.80, p<0.001); sleep disorders; and HIV/AIDS. Multimorbidity was present in 38% of cases versus 15.5% of controls, and represented nearly a twofold increased risk for suicide., Conclusions: Although several individual conditions, for example, traumatic brain injury, were associated with high risk of suicide, nearly all physical health conditions increased suicide risk, even after adjustment for potential confounders. In addition, having multiple physical health conditions increased suicide risk substantially. These data support suicide prevention based on the overall burden of physical health., (Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To examine and compare the arousability threshold and fall risk upon awakening of doxepin (6 mg) versus zolpidem (10 mg)., Methods: A total of 52 healthy adult males were included in a double-blind, placebo-controlled, four-way crossover study. The experimental procedure included four nights with polysomnography in the lab (zolpidem, doxepin, and their respective placebo conditions). Arousability was measured using an auditory awakening threshold delivered at the peak-plasma concentration for the active hypnotics and at matched times for the respective placebo conditions. Fall risk during the night was measured following awakening using the Berg Balance Scale and the Tandem Walk Task., Results: Both arousability and fall risk were lower in the doxepin condition compared to the zolpidem condition. Furthermore, arousability and fall risk for doxepin did not differ significantly from the placebo conditions. A significantly greater proportion of participants in the zolpidem condition (63.5%) did not wake until receiving the loudest tone (110 dB) as compared to the doxepin (17.6%) and placebo conditions (17.3%, 5.8%)., Conclusions: Results suggest that zolpidem has greater risks for balance and awakening threshold compared with low-dose doxepin. Future prospective studies should extend results to clinical samples with population-level risk of injury and arousability., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: To examine the real-world effectiveness of benzodiazepine receptor agonists (BzRAs) by quantifying response and remission rates in a clinical sample receiving chronic BzRA treatment for insomnia., Methods: Participants were outpatients (N = 193; 72% female; 55.2 ± 11.1 year) who had an insomnia diagnosis per medical records, and who were taking a therapeutic dose of BzRA for their insomnia. Endpoints were nocturnal sleep disturbance and Insomnia Severity Index (ISI) scores. A reduction meeting the criterion for the minimally important difference in ISI scores (change ≥ 6) constituted "response"; "remission" was inferred when symptoms fell below the clinical cutoff (ISI < 11)., Results: Most participants (71%) used BzRAs at least 5 nights per week. Mean ISI scores were significantly lower (t = 22.31; p < .01) while on BzRAs than when untreated, but remained in the clinical range (mean = 11.0; standard deviation = 5.7). Although 76.7% responded to treatment, only 47.7% remitted. The majority (68.9%) of participants had a sleep-onset latency > 30 minutes and/or wake-time after sleep onset > 60 minutes while on BzRAs. After controlling for gender and insomnia severity when untreated, odds of insomnia persistence despite BzRA use were 2 times higher in patients with comorbid medical [odds ratio (OR) = 2.39; 95% confidence interval (CI) = 1.20% to 4.77%; p < .05] and psychiatric disorders (OR = 2.24; 95% CI = 1.21% to 4.13%; p < .05)., Conclusions: This is the first study to distinguish between response and remission in insomnia patients taking BzRAs. Findings suggest that while many insomnia patients respond to chronic BzRA treatment, most do not remit. Remission rates are particularly low for comorbid insomnia, the most prevalent phenotype of the disorder., (© Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Current US guidelines recommend the Asthma Control Test (ACT) for assessing disease control and selecting treatment., Objective: The goal of this study was to prospectively assess the ACT and its component questions for their utility in predicting the risk of severe asthma exacerbations., Methods: Individuals were participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, and those included in the current analysis had the following characteristics: age 18 years or more, physician-diagnosed asthma, and longitudinal care received at a large health system in southeastern Michigan. Study participants underwent a baseline evaluation, which included answering the ACT. A severe asthma exacerbation was defined as one requiring oral steroids, an emergency department visit, or inpatient admission. Receiver-operator characteristic curves were used to measure and compare the predictive utility of the ACT and its component questions for severe asthma exacerbations., Results: Of 1180 participants, 354 (30.0%) experienced a severe asthma exacerbation within 6 months of their baseline evaluation. When compared with the individual questions that composed the ACT, the composite score was significantly better at predicting severe exacerbations with 1 exception; the composite ACT score and the question assessing rescue medication use were not significantly different (P = .580). Pharmacy-based records of metered-dose inhaler short-acting beta-agonist use and asthma severity were also not significantly different from the composite ACT score., Conclusions: Our study demonstrates that although the ACT is modestly predictive for exacerbations, the composite score may not be superior to assessing rescue medication use alone for predicting the risk of severe asthma exacerbations., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence of hypertension. NZBWF1 (SLE-Hyp) mice develop hypertension that can be prevented by modulating T cells. The peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) decreases renal damage and improves renal function in a model of SLE without hypertension (MRL/lpr). However, it is not known whether Ac-SDKP prevents hypertension in NZBWF1 mice. We hypothesized that in SLE-Hyp, Ac-SDKP prevents hypertension and renal damage by modulating T cells. Animals were divided into four groups: (1) control + vehicle, (2) control + Ac-SDKP, (3) SLE + vehicle, and (4) SLE + Ac-SDKP Systolic blood pressure (SBP), albuminuria, renal fibrosis, and T-cell phenotype were analyzed. SBP was higher in SLE compared to control mice and was not decreased by Ac-SDKP treatment. Half of SLE mice developed an acute and severe form of hypertension accompanied by albuminuria followed by death. Ac-SDKP delayed development of severe hypertension, albuminuria, and early mortality, but this delay did not reach statistical significance. Ac-SDKP prevented glomerulosclerosis, but not interstitial fibrosis in SLE-Hyp mice. SLE-Hyp mice showed a decrease in helper and cytotoxic T cells as well as an increase in double negative lymphocytes and T helper 17 cells, but these cells were unaffected by Ac-SDKP In conclusion, Ac-SDKP prevents kidney damage, without affecting blood pressure in an SLE animal model. However, during the acute relapse of SLE, Ac-SDKP might also delay the manifestation of an acute and severe form of hypertension leading to early mortality. Ac-SDKP is a potential tool to treat renal damage in SLE-Hyp mice., (© 2017 Henry Ford Health System. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Objective: This exploratory study assessed health literacy among urban African-American high school students to improve understanding of the association between adolescent health literacy and asthma., Methods: We conducted a secondary data analysis of the control group (n = 181) of the Puff City randomized controlled trial (2006-2010), a web-based intervention to promote asthma management among students, grades 9 through 12. A validated self-report 3-item health literacy screening instrument was completed at final online follow-up survey. Logistic regression was used to explore the association between health literacy, demographic characteristics, quality of life, asthma management, and health care utilization., Results: Multivariate analysis revealed that an overall inadequate health literacy score was associated with students who were more likely to be younger (OR 0.61; 95% CI 0.44-0.84), not on Medicaid (OR 0.36; 95% CI 0.17-0.76), have at least one hospitalization (OR 1.29; 95% CI 1.07-1.56); and a lower overall quality of life (OR 0.75; 95% CI 0.59-0.95). Those lacking confidence in filling out medical forms, needing help reading hospital materials, and having difficulty understanding written information were more likely to not have a rescue inhaler (OR 0.49; 95% CI 0.25-0.94), have one or more emergency visits (OR 1.21 95% CI 1.02-1.43), and one or more hospitalizations (OR 1.19; 95% CI 1.01-1.41), respectively., Conclusions: The findings indicate a significant association between inadequate health literary and suboptimal asthma management. It is important to advance understanding of adolescent health literacy, especially those at-risk, as they assume asthma self-management tasks and move toward independent adult self-care., Competing Interests: Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Connecting tubule glomerular feedback (CTGF) is a mechanism where an increase in sodium (Na) concentration in the connecting tubule (CNT) causes the afferent arteriole (Af-Art) to dilate. We recently reported that aldosterone within the CNT lumen enhances CTGF via a nongenomic effect involving GPR30 receptors and sodium/hydrogen exchanger (NHE), but the signaling pathways of this mechanism are unknown. We hypothesize that aldosterone enhances CTGF via cAMP/protein kinase A (PKA) pathway that activates protein kinase C (PKC) and stimulates superoxide (O 2 - ) production. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing the CNT luminal NaCl. We found that the main effect of aldosterone was to sensitize CTGF and we analyzed data by comparing NaCl concentration in the CNT perfusate needed to achieve half of the maximal response (EC 50 ) was 37.0 ± 2.0 mmol/l; addition of aldosterone (10 50 mol/l) to the CNT lumen decreased EC -8 to 19.3 ± 1.3 mmol/l (P ≤ 0.001 vs. Control). The specific adenylyl cyclase inhibitor 2',3'-dideoxyadenosine (ddA; 2 × 10 50 mol/l) and the PKA inhibitor H-89 dihydrochloride hydrate (H-89; 2 × 10 -4 mol/l) prevented the aldosterone effect. The selective PKC inhibitor GF109203X (10 -6 mol/l) also prevented EC -8 mol/l) also prevented EC 50 reduction caused by aldosterone. CNT intraluminal addition of O 2 mol/l) blocked the aldosterone effect. We conclude that aldosterone inside the CNT lumen enhances CTGF via a cAMP/PKA/PKC pathway and stimulates O - scavenger tempol (10 -4 mol/l) blocked the aldosterone effect. We conclude that aldosterone inside the CNT lumen enhances CTGF via a cAMP/PKA/PKC pathway and stimulates O 2 - generation and this process may contribute to renal damage by increasing glomerular capillary pressure., (Copyright © 2016 the American Physiological Society.)

Galectin-3 (Gal-3), a member of the β-galactoside lectin family, has an important role in immune regulation. In hypertensive rats and heart failure patients, Gal-3 is considered a marker for an unfavorable prognosis. Nevertheless, the role and mechanism of Gal-3 action in hypertension-induced target organ damage are unknown. We hypothesized that, in angiotensin II (ANG II)-induced hypertension, genetic deletion of Gal-3 prevents left ventricular (LV) adverse remodeling and LV dysfunction by reducing the innate immune responses and myocardial fibrosis. To induce hypertension, male C57BL/6J and Gal-3 knockout (KO) mice were infused with ANG II (3 μg·min -1 ·kg -1 sc) for 8 wk. We assessed: 1) systolic blood pressure by plethysmography, 2) LV function and remodeling by echocardiography, 3) myocardial fibrosis by histology, 4) cardiac CD68 + macrophage infiltration by histology, 5) ICAM-1 and VCAM-1 expression by Western blotting, 6) plasma cytokines, including interleukin-6 (IL-6), by enzyme-linked immunosorbent assay, and 7) regulatory T (T reg ) cells by flow cytometry as detected by their combined expression of CD4, CD25, and FOXP3. Systolic blood pressure and cardiac hypertrophy increased similarly in both mouse strains when infused with ANG II. However, hypertensive C57BL/6J mice suffered impaired ejection and shortening fractions. In these mice, the extent of myocardial fibrosis and macrophage infiltration was greater in histological sections, and cardiac ICAM-1, as well as plasma IL-6, expression was higher as assessed by Western blotting. However, all these parameters were blunted in Gal-3 KO mice. Hypertensive Gal-3 KO mice also had a higher number of splenic T reg lymphocytes. In conclusion, in ANG II-induced hypertension, genetic deletion of Gal-3 prevented LV dysfunction without affecting blood pressure or LV hypertrophy. This study indicates that the ANG II effects are, in part, mediated or triggered by Gal-3 together with the related intercellular signaling (ICAM-1 and IL-6), leading to cardiac inflammation and fibrosis., (Copyright © 2016 the American Physiological Society.)